Recent studies of herpes simplex virus infections of the nervous system have largely difined the progression of the infection as it moves from a peripheral site of infection through the peripheral nerves via axoplasmic flow, to the sensory ganglia into the spinal cord and finally to the brain. This progression can be altered at the sensory ganglia where the virus can establish a latent infection in the neurons. This proposal is basically concerned with obtaining information to further our understanding of the pathogenesis and consequences of herpes simplex virus infections of the nervous system. We have developed and done some preliminary characterizations of a tissue culture model of rat skin-dorsal root ganglia. We propose to further characterize the ultrastructural and electrophysiology of this model. Once the normal ultrastructure of the skin and DRG tissue has been determined, we shall study the effects that herpes simplex virus infection has upon these normal ultrastructural and electrophysiological characteristics. Finally, we shall determine what effect 1) antiviral-antibody, 2) antibody-dependent cellular cytotoxicity (ADCC) and 3) cellular cytotoxicity has on the pathogenesis of the virus. We are particularly interested to determine if any of these host's immune defense mechanisms either by themselves or in combination can establish a latent infection of the neurons.